tbuckley/cabot-search huggingface dataset:
Fatty Acids Invigorate Tumor-Resident Memory T Cells
Authors: Paramita Chakraborty, Stephanie Mills, Shikhar Mehrotra
Journal: Cancer Research (2023)

Abstract Tissue-resident memory T cells (Trm) represent a diverse cell type with tissue-specific gene signatures that can operate as both effector and memory T cells. Trm cells play a crucial role in immune defense against infections and cancer. Recently, Trm cells have become appreciated as a critical responder to checkpoint immunotherapy and as a biomarker of favorable outcomes in cancer. Hence, it is of great clinical and therapeutic importance to investigate how Trm cells can be manipulated transcriptionally, epigenetically, or metabolically to improve their longevity and function. In this issue of Cancer Research, Feng and colleagues demonstrate that the transcription factor SCML4 is essential for the development and polyfunctionality of Trm cells. Fatty acids mediated the upregulation of SCML4 via the mTOR–IRF4–PRDM1 signaling pathway, which significantly enhanced tumor control in multiple aggressive murine tumor models and was associated with a favorable prognosis for patients with cancer. The findings also suggest that SCML4-mediated engagement of the HBO1–BRPF2–ING4 complex epigenetically reprogramed Trm cells by increasing the expression of several survival- and effector-associated molecules while blocking the expression of checkpoint inhibitors. Overall, Feng and colleagues highlight a critical activation target for tumor immunotherapy and provide a molecular perspective on recruiting antitumor Trm cells to the tumor niche by regulating fatty acids. See related article by Feng et al., p. 3368
Suicide Ideation, Plans, and Attempts Among Military Veterans vs Nonveterans With Disability
Authors: Rebecca K. Blais, Zhigang Xie, Anne V. Kirby, Nicole M. Marlow
Journal: JAMA Network Open (2023)

Importance People with disability are at heightened risk for suicide ideation, planning, and attempt, with risk growing as the number of disabling limitations increases. Military veterans have higher rates of suicide deaths and disability relative to nonveterans. Objective To evaluate whether veteran status is associated with greater risk for suicide in those with disability. Design, Setting, and Participants This survey study used cross-sectional self-reported data from US adults who participated in the 2015-2020 National Survey on Drug Use and Health. Data were weighted to represent the population. Data analysis was conducted from July to August 2022. Main Outcomes and Measures Suicide ideation, planning, and attempt served as primary outcomes. Disability status (present or absent) and number of disabling limitations (1, 2, or ≥3) served as factors. Veteran status was determined based on self-report (veteran or nonveteran). Multivariable logistic regression examined suicide ideation, planning, and attempt as a function of veteran status and disability variables. Results Participants included 231 099 US veterans and nonveterans, representing 236 551 727 US adults, of whom 20.03% (weighted n = 47 397 876) reported a disabling limitation, 8.92% were veterans (weighted n = 21 111 727; 16.0% aged 35-49 years; 91.0% men; 6.7% Hispanic; 10.9% non-Hispanic Black; and 78.4% non-Hispanic White) and 91.08% were nonveterans (weighted n = 215 440 000; 25.4% aged 35-49 years; 44.0% male; 16.5% Hispanic; 11.7% non-Hispanic Black; and 63.3% non-Hispanic White). Overall, 4.39% reported suicide ideation, planning, or attempt (weighted n = 10 401 065). Among those with no disability, veteran status was associated with higher risk of suicide planning (adjusted odds ratio [AOR], 1.71; 95% CI, 1.17-2.49). Among those with 1 or 2 disabling limitations, being a veteran was associated with a lower risk of suicide planning (AOR, 0.57; 95% CI, 0.34-0.95) and history of attempt (AOR, 0.46; 95% CI, 0.24-0.88). Conclusions and Relevance In this study of how suicide risk differs as a function of disability and veteran status, risk for death by suicide was lower among veterans with disability relative to nonveterans with disability. Veteran status may mitigate risk for suicide given increased receipt of more disability-related care through the Department of Veterans Affairs. Further research would extend this line of inquiry by examining the cause and type of disability as well as perceptions of disability on self-worth. It is possible that physical wounds of war are protective because of the meaning and value of service to one’s country.
Risk factors for incident venous thromboembolism in patients with renal tumor and inferior vena cava tumor thrombus: a retrospective case–control study
Authors: Hanfeng Wang, Xinran Chen, Kailong Wang, Wenzhe Cao, Qingbo Huang, Cheng Peng, Tongyu Jia, Qiyang Liang, Baojun Wang, Liangyou Gu, Xu Zhang, Xin Ma
Journal: International Journal of Surgery (2023)

Venous thromboembolism (VTE) is a principal cause of mortality and adverse oncologic outcomes in patients with renal tumor and inferior vena cava tumor thrombus (RT-IVCTT). However, the preoperative thrombotic risk factors in these patients remain not fully characterized.
A high risk of postoperative periprosthetic femoral fracture in Dorr type C femurs: a retrospective cohort study with 10-year follow-up data and a preliminary monochromatic image analysis
Authors: Mingyang Li, Yi Zeng, Yong Nie, Kai Liao, Fuxing Pei, Jing Yang, Huiqi Xie, Bin Shen
Journal: International Journal of Surgery (2023)

Background: We applied Anatomique Benoist Girard II (ABG II) stems for total hip arthroplasty (THA) in some Dorr type C femurs as early attempts. Here, we compared the long-term follow-up results between ABG II stems and the “well-performing” Corail stems and their monochromatic images. Methods: Among 3214 primary THA records, 43 short ABG II stems and 67 standard-length Corail stems implanted in Dorr type C femurs were eligible and enrolled in this retrospective cohort study, with a mean follow-up of 10.3 years. Revision rates, Harris hip scores, and radiologic signs were compared. Spectral CT scans from a representative sample were obtained, and monochromatic images were reconstructed. A quantitative method was developed to measure the volume of the gap around stems. Patient-specific finite element analysis was conducted to investigate the strains. Results: The revision rate of ABG II stems was significantly higher than that of Corail stems (21% vs. 3%, P &lt;0.05). In the monochromatic images, fewer spot-weld signs (2.15 vs. 3.38, P &lt;0.05) and wider gaps around stems (1.64 cm 3 vs. 0.13 cm 3 , P &lt;0.05) were observed on average in the ABG II group. The mean maximum principal strains of the proximal femurs in the ABG II group were close to the yield strains and significantly larger than those in the Corail group (0.0052 vs. 0.0011, P &lt;0.05). Conclusions: There was a high risk of postoperative periprosthetic femoral fracture for ABG II stems in Dorr type C femurs. Monochromatic images provided some insight into the failure mechanism. Level of Evidence: III
ChatGPT indicates the path and initiates the research to open up the black box of artificial intelligence
Authors: Chiranjib Chakraborty, Manojit Bhattacharya, Md. Aminul Islam, Govindasamy Agoramoorthy
Journal: International Journal of Surgery (2023)

Chakraborty, Chiranjib PhD; Bhattacharya, Manojit PhD; Islam, Md. Aminul; Agoramoorthy, Govindasamy PhD Author Information
Asymptomatic Patients With Brugada ECG Pattern: Long-Term Prognosis From a Large Prospective Study
Authors: Fiorenzo Gaita, Natascia Cerrato, Carla Giustetto, Annamaria Martino, Laura Bergamasco, Michele Millesimo, Lorella Barbonaglia, Paula Carvalho, Domenico Caponi, Andrea Saglietto, Giacomo Bonacchi, Francesca Bianchi, Elisa Silvetti, Cinzia Crescenzi, Stefano Canestrelli, Melissa De Maio, Gaetano Maria De Ferrari, Giuseppe Musumeci, Francesco Rametta, Marco Scaglione, Leonardo Calò
Journal: Circulation (2023)

Brugada syndrome poses significant challenges in terms of risk stratification and management, particularly for asymptomatic patients who comprise the majority of individuals exhibiting Brugada ECG pattern (BrECG). The aim of this study was to evaluate the long-term prognosis of a large cohort of asymptomatic patients with BrECG.
A Small Molecule with Big Impact: MRTX1133 Targets the KRASG12D Mutation in Pancreatic Cancer
Authors: Daoyan Wei, Liang Wang, Xiangsheng Zuo, Anirban Maitra, Robert S. Bresalier
Journal: Clinical Cancer Research (2023)

Abstract KRAS mutations drive oncogenic alterations in numerous cancers, particularly in human pancreatic ductal adenocarcinoma (PDAC). About 93% of PDACs have KRAS mutations, with G12D (∼42% of cases) and G12V (∼32% of cases) being the most common. The recent approval of sotorasib (AMG510), a small-molecule, covalent, and selective KRASG12C inhibitor, for treating patients with non–small cell lung cancer represents a breakthrough in KRAS targeted therapy. However, there is a need to develop other much-needed KRAS-mutant inhibitors for PDAC therapy. Notably, Mirati Therapeutics recently developed MRTX1133, a small-molecule, noncovalent, and selective KRASG12D inhibitor through extensive structure-based drug design. MRTX1133 has demonstrated potent in vitro and in vivo antitumor efficacy against KRASG12D-mutant cancer cells, especially in PDAC, leading to its recent initiation of a phase I/II clinical trial. Here, we provide a summary of the recent advancements related to the use of MRTX1133 for treating KRASG12D-mutant PDAC, focusing on its efficacy and underlying mechanistic actions. In addition, we discuss potential challenges and future directions for MRTX1133 therapy for PDAC, including overcoming intrinsic and acquired drug resistance, developing effective combination therapies, and improving MRTX1133’s oral bioavailability and target spectrum. The promising results obtained from preclinical studies suggest that MRTX1133 could revolutionize the treatment of PDAC, bringing about a paradigm shift in its management.
CD24hiCD27+ Bregs within Metastatic Lymph Nodes Promote Multidrug Resistance in Breast Cancer
Authors: Huanhuan Huang, Yao Yao, Lesang Shen, Jingxin Jiang, Ting Zhang, Jia Xiong, Jiaxin Li, Shanshan Sun, Siwei Zheng, Fang Jia, Jun Zhou, Xiuyan Yu, Wuzhen Chen, Jun Shen, Wenjie Xia, Xuan Shao, Qingqing Wang, Jian Huang, Chao Ni
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Axillary lymph nodes (LN) are the primary and dominant metastatic sites in breast cancer. However, the interaction between tumor cells and immune cells within metastatic LNs (mLN) remains poorly understood. In our study, we explored the effect of CD24hiCD27+ regulatory B cells (Breg) within mLNs on orchestrating drug resistance of breast cancer cells. Experimental Design: We collected mLN samples from patients with breast cancer who had received standard neoadjuvant therapy (NAT) and analyzed the spatial features of CD24hiCD27+ Bregs through multicolor immunofluorescence staining. The effect of CD24hiCD27+ Bregs on drug resistance of breast cancer cells was evaluated via in vitro experiments. A mouse model with mLNs was used to evaluate the strategies with blocking the interactions between Bregs and breast cancer for improving tumor regression within mLNs. Results: In patients with breast cancer who had received NAT, there is a close spatial correlation between activated CD24hiCD27+ Bregs and residual tumor cells within mLNs. Mechanistically, CD24hiCD27+ Bregs greatly enhance the acquisition of multidrug resistance and stem-like features of breast cancer cells by secreting IL6 and TNFα. More importantly, breast cancer cells further promote the activation of CD24hiCD27+ Bregs via CD40L-dependent and PD-L1–dependent proximal signals, forming a positive feedback pattern. PD-L1 blockade significantly attenuates the drug resistance of breast cancer cells induced by CD24hiCD27+ Bregs, and addition of anti-PD-L1 antibody to chemotherapy improves tumor cell remission in mLNs. Conclusions: Our study reveals the pivotal role of CD24hiCD27+ Bregs in promoting drug resistance by interacting with breast cancer cells in mLNs, providing novel evidence for an improved strategy of chemoimmunotherapy combination for patients with breast cancer with mLNs.
The value of manual backward contact tracing to control COVID-19 in practice, the Netherlands, February to March 2021: a pilot study
Authors: Timo Louis Boelsums, Inge Anna Theresia van de Luitgaarden, Jane Whelan, Hanna Poell, Charlotte Maria Hoffman, Ewout Fanoy, Maaike Buskermolen, Jan Hendrik Richardus
Journal: Eurosurveillance (2023)

Background Contact tracing has been a key component of COVID-19 outbreak control. Backward contact tracing (BCT) aims to trace the source that infected the index case and, thereafter, the cases infected by the source. Modelling studies have suggested BCT will substantially reduce SARS-CoV-2 transmission in addition to forward contact tracing. Aim To assess the feasibility and impact of adding BCT in practice. Methods We identified COVID-19 cases who were already registered in the electronic database between 19 February and 10 March 2021 for routine contact tracing at the Public Health Service (PHS) of Rotterdam-Rijnmond, the Netherlands (pop. 1.3 million). We investigated if, through a structured questionnaire by dedicated contact tracers, we could trace additional sources and cases infected by these sources. Potential sources identified by the index were approached to trace the source’s contacts. We evaluated the number of source contacts that could be additionally quarantined. Results Of 7,448 COVID-19 cases interviewed in the study period, 47% (n = 3,497) indicated a source that was already registered as a case in the PHS electronic database. A potential, not yet registered source was traced in 13% (n = 979). Backward contact tracing was possible in 62 of 979 cases, from whom an additional 133 potential sources were traced, and four were eligible for tracing of source contacts. Two additional contacts traced had to stay in quarantine for 1 day. No new COVID-19 cases were confirmed. Conclusions The addition of manual BCT to control the COVID-19 pandemic did not provide added value in our study setting.
Identification of glycogene-based prognostic signature as a potential biomarker and therapeutic target in sarcopenia
Authors: Dong Xu Chen, Yi Da Wang
Journal: International Journal of Surgery (2023)

aDepartment of Anesthesiology, West China Second Hospital of Sichuan University, Sichuan Province, Chengdu, 610041, China bKey Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education cKey Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, Collage of Life Science, Sichuan University, Chengdu, China Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: Department of Anesthesiology, West China Second Hospital of Sichuan University, Sichuan Province, Chengdu, 610041, China. E-mail address: [email protected] (D. Chen). This is an open access article distributed under the Creative Commons Attribution-ShareAlike License 4.0, which allows others to remix, tweak, and build upon the work, even for commercial purposes, as long as the author is credited and the new creations are licensed under the identical terms. http://creativecommons.org/licenses/by-sa/4.0/
A commentary on ‘Addressing Africa’s outrageous neurosurgeons deficit: what could the problem be?’
Authors: Si-Un Frank Chiu, Kang Lu, Chong-Chi Chiu
Journal: International Journal of Surgery (2023)

aDepartment of Computer Science, Brown University, Providence, Rhode Island, USA bDepartment of Economics, Brown University, Providence, Rhode Island, USA cSchool of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan dDepartment of Neurosurgery, E-Da Cancer Hospital, I-Shou University, Kaohsiung, Taiwan eDepartment of Neurosurgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan fDepartment of General Surgery, E-Da Cancer Hospital, I-Shou University, Kaohsiung, Taiwan gDepartment of Medical Education and Research, E-Da Cancer Hospital, I-Shou University, Kaohsiung, Taiwan Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article Published online ■ ■ *Corresponding author. Address: No.21, Yi-Da Road, Jiao-Su Village, Yan-Chao District, Kaohsiung, 824, Taiwan, Tel: 886-76150022, Fax: 886-76150940. E-mail address: [email protected] (C-C. Chiu). This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0/
Comparative Discrimination of Life’s Simple 7 and Life’s Essential 8 to Stratify Cardiovascular Risk: Is the Added Complexity Worth It?
Authors: George Howard, Mary Cushman, Jessica Blair, Nicole R. Wilson, Ya Yuan, Monika M. Safford, Emily B. Levitan, Suzanne E. Judd, Virginia J. Howard
Journal: Circulation (2023)

Life's Simple 7 (LS7) is an easily calculated and interpreted metric of cardiovascular health based on 7 domains: smoking, diet, physical activity, body mass index, blood pressure, cholesterol, and fasting glucose. The Life's Essential 8 (LE8) metric was subsequently introduced, adding sleep metrics and revisions of the previous 7 domains. Although calculating LE8 requires additional information, we hypothesized that it would be a more reliable index of cardiovascular health.
The Place of Cannabinoids in the Treatment of Gynecological Pain
Authors: Justin Sinclair, Jason Abbott, Andrew Proudfoot, Mike Armour
Journal: Drugs (2023)

Cannabis sativa (L), a plant with an extensive history of medicinal usage across numerous cultures, has received increased attention over recent years for its therapeutic potential for gynecological disorders such as endometriosis, chronic pelvic pain, and primary dysmenorrhea, due at least in part to shortcomings with current management options. Despite this growing interest, cannabis inhabits an unusual position in the modern medical pharmacopoeia, being a legal medicine, legal recreational drug, and an illicit drug, depending on jurisdiction. To date, the majority of studies investigating cannabis use have found that most people are using illicit cannabis, with numerous obstacles to medical cannabis adoption having been identified, including outdated drug-driving laws, workplace drug testing policies, the cost of quality-assured medical cannabis products, a lack of cannabis education for healthcare professionals, and significant and persistent stigma. Although currently lacking robust clinical trial data, a growing evidence base of retrospective data, cohort studies, and surveys does support potential use in gynecological pain conditions, with most evidence focusing on endometriosis. Cannabis consumers report substantial reductions in pelvic pain, as well as common comorbid symptoms such as gastrointestinal disturbances, mood disorders such as anxiety and depression, and poor sleep. Substitution effects were reported, with >50% reduction or cessation in opioid and/or non-opioid analgesics being the most common. However, a substantial minority report not disclosing cannabis consumption to their health professional. Therefore, while such deprescribing trends are potentially beneficial, the importance of medical supervision during this process is paramount given the possibility for withdrawal symptoms.Cannabis, whether purchased illicitly, or obtained through legal means, is commonly used by those with chronic pelvic pain, especially people with endometriosis. People report several benefits from using cannabis, including being able to reduce their normal medications including opioid based painkillers, but often don’t tell their health professional about this. This could lead to issues with withdrawal symptoms, so clinicians should be aware of the high prevalence of use of cannabis in this population.
Development and validation of an interpretable Markov-embedded multilabel model for predicting risks of multiple postoperative complications among surgical inpatients: a multicenter prospective cohort study
Authors: Xiaochu Yu, Luwen Zhang, Qing He, Yuguang Huang, Peng Wu, Shijie Xin, Qiang Zhang, Shengxiu Zhao, Hong Sun, Guanghua Lei, Taiping Zhang, Jingmei Jiang
Journal: International Journal of Surgery (2023)

Background: When they encounter various highly related postoperative complications, existing risk evaluation tools that focus on single or any complications are inadequate in clinical practice. This seriously hinders complication management because of the lack of a quantitative basis. An interpretable multi-label model framework that predicts multiple complications simultaneously is urgently needed. Materials and Methods: We included 50,325 inpatients from a large multicenter cohort (2014–2017). We separated patients from one hospital for external validation and randomly split the remaining patients into training and internal validation sets. A MARKov-EmbeDded (MARKED) multi-label model was proposed, and three models were trained for comparison: binary relevance (BR), a fully connected network (FULLNET), and a deep neural network (DNN). Performance was mainly evaluated using the area under the receiver operating characteristic curve (AUC). We interpreted the model using Shapley Additive Explanations. Complication-specific risk and risk source inference were provided at the individual level. Results: There were 26,292, 6574, and 17,459 inpatients in the training, internal validation, and external validation sets, respectively. For the external validation set, MARKED achieved the highest average AUC (0.818, 95% confidence interval: 0.771–0.864) across eight outcomes (compared with BR, 0.799 [0.748–0.849], FULLNET, 0.806 [0.756–0.856], and DNN, 0.815 [0.765–0.866]). Specifically, the AUCs of MARKED were above 0.9 for cardiac complications (0.927 [0.894–0.960]), neurological complications (0.905 [0.870–0.941]), and mortality (0.902 [0.867–0.937]). Serum albumin, surgical specialties, emergency case, American Society of Anesthesiologists score, age, and sex were the six most important preoperative variables. The interaction between complications contributed more than the preoperative variables, and formed a hierarchical chain of risk factors, mild complications, and severe complications. Conclusion: We demonstrated the advantage of MARKED in terms of performance and interpretability. We expect that the identification of high-risk patients and inference of the risk source for specific complications will be valuable for clinical decision-making.
Food-borne botulism outbreak during the Rugby World Cup linked to marinated sardines in Bordeaux, France, September 2023
Authors: Léa Courtot-Melciolle, Marine Jauvain, Mona Siefridt, Renaud Prevel, Olivia Peuchant, Olivier Guisset, Gaëlle Mourissoux, Laure Diancourt, Christelle Mazuet, Gauthier Delvallez, Alexandre Boyer, Arthur Orieux
Journal: Eurosurveillance (2023)

In September 2023, a botulism outbreak affecting 15 individuals occurred in Bordeaux, France, during the Rugby World Cup. We report on eight individuals from four different countries on two continents admitted to the intensive care unit at our hospital, where six required invasive mechanical ventilation. Cases reported consuming locally produced canned sardines at a restaurant. This report highlights the importance of rapid, worldwide alerts from health authorities to prevent severe consequences of such outbreaks, particularly during events attracting international visitors.
Reducing Pediatric Hospital-Acquired Venous Thromboembolism—Overcoming Challenges Using Quality Improvement
Authors: Jerome Gene Chen
Journal: JAMA Network Open (2023)

Shannon C. Walker, MD; Benjamin French, PhD; Ryan P. Moore, MS; Henry J. Domenico, MS; Jonathan P. Wanderer, MD, MPhil; Amanda S. Mixon, MD, MS, MSPH; C. Buddy Creech, MD, MPH; Daniel W. Byrne, MS; Allison P. Wheeler, MD, MSCI